Specific patterns of oncogene activation in transplacentally induced tumors.
Specific patterns of oncogene activation in transplacentally induced tumors.
复制标题
经胎盘诱导的肿瘤中癌基因激活的特定模式。
DOI：
10.1073/pnas.87.2.718
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Barbacid,M
中科院分区：
文献类型：
--
作者：
Sukumar,S;Barbacid,M
大鼠经胎盘暴露于单一剂量的直接作用致癌物甲基亚硝脲(MNU)可导致多种神经外胚层、上皮和间充质来源的肿瘤。对这些肿瘤中存在的致癌基因的分子分析显示出惊人的组织特异性。研究发现，neu癌基因在来自外周神经系统(PNS)的肿瘤中可被重复激活，但在来自中枢神经系统(CNS)的肿瘤中则不被激活。在PNS和CNS来源的肿瘤中均未发现ras癌基因。然而，Ha-ras癌基因在3例乳腺癌中均有表达，Ki-ras癌基因在5例肾间叶性肿瘤中均有表达。这些结果表明，激活的癌基因在体内的表型表达不是一个随机的过程，提示正常的发育程序可能在化学致癌物对特定癌基因的激活调控中发挥重要作用。PCR分析显示，在这些经胎盘诱导的肿瘤中检测到的每个ras癌基因都被第12密码子第二碱基的G-A转换激活。由于G-A转换是MNU诱导的首选突变，这些ras癌基因可能在胚胎发育过程中被MNU直接靶向。
Transplacental exposure of rats to a single dose of the direct acting carcinogen methylnitrosourea (MNU) results in the induction of a variety of neoplasias of neuroectodermal, epithelial, and mesenchymal origin. Molecular analysis of the oncogenes present in these tumors revealed a striking degree of tissue specificity. neu oncogenes were found to be reproducibly activated in tumors derived from the peripheral nervous system (PNS), but not in those arising from the central nervous system (CNS). No ras oncogenes were found in either PNS- or CNS-derived tumors. However, Ha-ras oncogenes were detected in each of three mammary carcinomas and Ki-ras oncogenes were present in each of five kidney mesenchymal tumors. These results illustrate that phenotypic expression of activated oncogenes in vivo is not a random process and suggest that normal developmental programs may play an important role in modulating the activation of specific oncogenes by chemical carcinogens. PCR analysis revealed that each of the ras oncogenes detected in these transplacentally induced tumors became activated by the same G----A transition in the second base of codon 12. Since G----A transitions are the preferred mutations induced by MNU, it is likely that these ras oncogenes may have been directly targeted by MNU during embryonic development.